GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance

NCT ID: NCT01381328

Last Updated: 2013-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-12-31

Study Completion Date

2013-09-30

Brief Summary

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The purpose of this study is to correlate the different patterns of resistance mutations observed in vivo in patients failing RAL treatment with the fold-change resistance determined by the phenotypic assay.

Detailed Description

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The secondary objectives are, as follows:

* to establish standardised genotypic assay for the HIV-1 pol gene region (region of interest, sensitivity, mutations involved as primary or compensatory changes, role of polymorphism present at baseline).
* to reach consensus on the algorithm interpretation of in house ex-vivo genotypic evaluations.
* to assess the genetic changes in RAL-failing patients under continuous drug pressure or drug discontinuation (dynamics of the reversion of resistance mutations).
* to evaluate in RAL resistant HIV-1 variants the changes in replication capacity (RC) (baseline vs. following-timepoints).
* to evaluate the immunological and virological trend associated with a raltegravir-regimen failure.

Conditions

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HIV-1 Infected Patients Fold-change Resistance Resistance Mutations

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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RAL Group

HIV-1 infected patients failing to a RALTEGRAVIR-containing regimen

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Adult (at least 18 years of age) treatment-experienced, HIV-infected subjects of either sex and of any race, failing to a RAL-containing regimen will be enrolled in the study

Exclusion Criteria

* none
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS San Raffaele

OTHER

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Università Vita-Salute San Raffaele

OTHER

Sponsor Role lead

Responsible Party

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Elisabetta Carini

Professor Massimo Clementi

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Massimo Clementi, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Vita-Salute San Raffaele Laboratory of Microbiology and Virology

Antonella Castagna, MD

Role: STUDY_DIRECTOR

Department of Infectious Diseases, IRCCS San Raffaele Hospital

Locations

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Department of Infectious Diseases, IRCCS San Raffaele Hospital

Milan, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Antonella Castagna, MD

Role: CONTACT

0039022643 ext. 7934

Elisabetta Carini, Msc

Role: CONTACT

0039022643 ext. 7934

Facility Contacts

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Antonella Castagna, MD

Role: primary

0039022643 ext. 7934

Elisabetta Carini, MSc

Role: backup

0039022643 ext. 7934

References

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Engelman A, Mizuuchi K, Craigie R. HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell. 1991 Dec 20;67(6):1211-21. doi: 10.1016/0092-8674(91)90297-c.

Reference Type BACKGROUND
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Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov. 2005 Mar;4(3):236-48. doi: 10.1038/nrd1660.

Reference Type BACKGROUND
PMID: 15729361 (View on PubMed)

Anker M, Corales RB. Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. doi: 10.1517/13543784.17.1.97.

Reference Type BACKGROUND
PMID: 18095922 (View on PubMed)

Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.

Reference Type BACKGROUND
PMID: 17434401 (View on PubMed)

Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65. doi: 10.1056/NEJMoa0708978.

Reference Type BACKGROUND
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Canducci F, Sampaolo M, Marinozzi MC, Boeri E, Spagnuolo V, Galli A, Castagna A, Lazzarin A, Clementi M, Gianotti N. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS. 2009 Feb 20;23(4):455-60. doi: 10.1097/QAD.0b013e328323da60.

Reference Type BACKGROUND
PMID: 19165083 (View on PubMed)

Nakahara K, Wakasa-Morimoto C, Kobayashi M, Miki S, Noshi T, Seki T, Kanamori-Koyama M, Kawauchi S, Suyama A, Fujishita T, Yoshinaga T, Garvey EP, Johns BA, Foster SA, Underwood MR, Sato A, Fujiwara T. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Antiviral Res. 2009 Feb;81(2):141-6. doi: 10.1016/j.antiviral.2008.10.007. Epub 2008 Nov 21.

Reference Type BACKGROUND
PMID: 19027039 (View on PubMed)

Kobayashi M, Nakahara K, Seki T, Miki S, Kawauchi S, Suyama A, Wakasa-Morimoto C, Kodama M, Endoh T, Oosugi E, Matsushita Y, Murai H, Fujishita T, Yoshinaga T, Garvey E, Foster S, Underwood M, Johns B, Sato A, Fujiwara T. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res. 2008 Nov;80(2):213-22. doi: 10.1016/j.antiviral.2008.06.012. Epub 2008 Jul 14.

Reference Type BACKGROUND
PMID: 18625269 (View on PubMed)

Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, Perno CF. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev. 2009 Jan-Mar;11(1):17-29.

Reference Type BACKGROUND
PMID: 19290031 (View on PubMed)

Malet I, Delelis O, Valantin MA, Montes B, Soulie C, Wirden M, Tchertanov L, Peytavin G, Reynes J, Mouscadet JF, Katlama C, Calvez V, Marcelin AG. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother. 2008 Apr;52(4):1351-8. doi: 10.1128/AAC.01228-07. Epub 2008 Jan 28.

Reference Type BACKGROUND
PMID: 18227187 (View on PubMed)

Menzo S, Monachetti A, Balotta C, Corvasce S, Rusconi S, Paolucci S, Baldanti F, Bagnarelli P, Clementi M. Processivity and drug-dependence of HIV-1 protease: determinants of viral fitness in variants resistant to protease inhibitors. AIDS. 2003 Mar 28;17(5):663-71. doi: 10.1097/01.aids.0000050852.71999.5f.

Reference Type BACKGROUND
PMID: 12646788 (View on PubMed)

Sichtig N, Sierra S, Kaiser R, Daumer M, Reuter S, Schulter E, Altmann A, Fatkenheuer G, Dittmer U, Pfister H, Esser S. Evolution of raltegravir resistance during therapy. J Antimicrob Chemother. 2009 Jul;64(1):25-32. doi: 10.1093/jac/dkp153. Epub 2009 May 14.

Reference Type BACKGROUND
PMID: 19447792 (View on PubMed)

Malet I, Delelis O, Soulie C, Wirden M, Tchertanov L, Mottaz P, Peytavin G, Katlama C, Mouscadet JF, Calvez V, Marcelin AG. Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. J Antimicrob Chemother. 2009 Apr;63(4):795-804. doi: 10.1093/jac/dkp014. Epub 2009 Feb 16.

Reference Type BACKGROUND
PMID: 19221102 (View on PubMed)

Other Identifiers

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Merck Sharp & Dohme Corp.

Identifier Type: OTHER

Identifier Source: secondary_id

Gepheral

Identifier Type: -

Identifier Source: org_study_id

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